The present invention relates to a novel adjuvant system that enhances the immune response to a broad spectrum of antigen targets. In this system aluminum adjuvants are associated (e.g., chemically linked) with ligands to C-type leptin (CTL) receptors. This system takes advantage of the efficiency of internalization by antigen presenting cells and historical safety of aluminum adjuvants and combines it with the ability of CTL receptor ligands to produce differential immune responses.
Aluminum adjuvants have a long history of safe use in human vaccines. Their adjuvant activity is thought to arise from making the antigen particulate in nature, causing irritation at the site of injection, and activation of the NALP3 inflammasome following internalization by antigen presenting cells (APCs). However, aluminum adjuvants alone are not always appropriate for a broad array of antigen targets because they typically stimulate a skewed Th2 type immune response. It has been documented for various antigens that formulation with aluminum-containing adjuvants stimulates production of IgG1 antibodies, typical for a Th2 response, while little or no IgG2a antibodies, typical of a Th1 response, are produced.
Therefore, there is a need to provide adjuvant compositions that have improved stability, increased potency and which provide an enhanced Th1 response.